Control of mechanical ventilation based on laryngopharyngeal muscle activity

ABSTRACT

The present invention relates to a system ( 1; 1 A) for use in connection with mechanical ventilation of a patient ( 3 ), provided by a ventilator ( 5 ). The system comprises a sensor arrangement ( 7; 7 A;  7 B) configured to register at least one signal (S LP ; S LP(TA) , S LP(CT) ; S e1-5 ; S e11-12 ), herein referred to as LP signal, related to muscular activity of at least one muscle ( 17, 19 ) in the laryngopharyngeal region ( 9 ) of said patient ( 3 ). Furthermore, the system comprises at least one control unit ( 11; 11 A,  11 B) configured to control the operation of said ventilator ( 5 ) based on said at least one LP signal, and/or to cause display of information related to said at least one LP signal on a display unit ( 13 A,  13 B) for monitoring said patient ( 3 ) and/or the operation of the ventilator ( 5 ).

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to the field of mechanical ventilation. Inparticular, the present invention relates to detection of signalsrelating to muscular activity of breathing-related muscles of a subject,and use of such signals in the control of a mechanical ventilatorproviding support ventilation to said subject.

Description of the Prior Art

In the field of mechanical ventilation, there are various techniques foradjusting the ventilation pattern provided by the ventilator to thepatient's own breathing efforts. Ventilation modes in which theventilator adapts the supply of breathing gas to detectable breathingefforts of a ventilated patient are generally referred to as modes ofassisted or supported ventilation. More commonly, a ventilator that isoperated in such a ventilation mode is said to provide supportventilation to the patient.

In recent years there has evolved techniques for neurally adjustedventilation, i.e. techniques in which the ventilation pattern providedto the patient by the ventilator is adapted to the breathing efforts ofthe patient by controlling the supply of breathing gas by the ventilatorbased on neurological signals indicating at least the points in time atwhich there is a desire of the patient to inhale and/or exhale. Anexample of such a technique is the now clinically well-establishedtechnique of Neurally Adjusted Ventilatory Assist (NAVA).

The act of taking a breath is controlled by the respiratory center ofthe brain, which decides the characteristics of each breath, timing andsize. The respiratory center sends a signal along the phrenic nerve,excites the diaphragm muscle cells, leading to muscle contraction anddescent of the diaphragm dome. As a result, the pressure in the airwaydrops, causing an inflow of air into the lungs.

With NAVA, the electrical activity of the diaphragm (Edi) is captured,fed to a NAVA-enabled ventilator and used to assist the patient'sbreathing in synchrony with and in proportion to the patient's ownbreathing efforts. As the work of the ventilator and the diaphragm iscontrolled by the same signal, coupling between the diaphragm and theNAVA-enabled ventilator is synchronized simultaneously.

The NAVA technology is further described in e.g. WO 1998/48877, WO1999/62580, WO 2006/131149, and WO 2008/131798.

The Edi is typically captured by measuring the electromyogram (EMG) ofthe contracting diaphragm, sometimes referred to as diaphragm EMG. TheEMG signals are then processed in various ways and a signalrepresentative of the Edi is calculated and used in the control of theNAVA-enabled ventilator, typically by controlling the supply ofbreathing gas to the patient in synchrony and in proportion to the Edi.

Typically, the EMG signals representative of said Edi signal aremeasured by means of an array of electrodes arranged along an esophagealcatheter inserted into the esophagus of the patient. Such a catheter isoften referred to as a NAVA catheter and is described in more detail infor example U.S. Pat. No. 5,671,752 and U.S. Pat. No. 7,021,310.

Instead or in addition to a NAVA catheter for picking up signals fromwithin the patient, a set of chest wall surface electrodes may be usedto record the diaphragm EMG from the surface of the skin of the patient.Just like the EMG signals picked up by the NAVA catheter, the diaphragmEMG recorded by means of such surface electrodes may be used to derive adiaphragm Edi signal of the patient, which Edi signal may be used in thecontrol of a NAVA-enabled ventilator operated in NAVA mode.

In some situations, the EMG signals registered by the NAVA catheter orthe chest wall surface electrodes are weak or not truly representativeof the Edi of the patient, thereby rendering NAVA ventilationunsuitable. One challenge within the field of NAVA ventilation isdetection and verification of such situations. Another challenge is howto best handle the situation in which absence of a reliable Edi signalcan be verified.

Yet another challenge within the field of NAVA ventilation is how tomake control of the ventilator more robust in situations in which theEdi signal alone does not provide sufficient or sufficiently reliableinformation on the physiological state or the desired respiratorypattern of the ventilated patient.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an improved or atleast alternative way of controlling a ventilator providing supportventilation to a patient. In particular, it is an object of theinvention to provide an improved or at least alternative way ofproviding neurally adjusted ventilatory assist (NAVA) to a patient,meeting one or more of the above-mentioned challenges of conventionalNAVA ventilation.

Another object of the invention is to provide an improved or at leastalternative bioelectric sensor arrangement for use during mechanicalventilation of a patient.

According to one aspect of the present invention there is provided asystem for use in connection with mechanical ventilation of a patient,provided by a ventilator. The system comprises a sensor arrangementconfigured to register at least one signal related to muscular activityof at least one muscle in the laryngopharyngeal region of the patient.Further, the system comprises at least one control unit configured tocontrol the operation of said ventilator based on said at least oneregistered signal, and/or to cause display of information related tosaid at least one registered signal on at least one display unit.

The at least one display unit may be a display unit of the ventilatorand/or a display unit of a stand-alone monitoring system for monitoringthe status of the patient and/or the operation of the ventilator. Thedisplay of information related to the registered signal may serve as adecision support to an operator who manually or partially manuallycontrols the operation of the ventilator based on e.g. informationdisplayed on said display unit, including but not limited to saidregistered signals.

Thus, the present invention presents a system allowing the operation ofa ventilator to be automatically or manually controlled based oninformation contained in a signal related to the muscular activity of atleast one muscle in the laryngopharyngeal region of the patient. Such asignal will hereinafter be referred to as a laryngopharyngeal signal (LPsignal). The muscular activity of some muscles in this region iscontrolled by the respiratory center of the brain and so indicative ofthe patient's efforts to breathe. Thus, the at least one LP signalregistered by the sensor arrangement and related to said muscularactivity provides information which alone or in combination with otherinformation indicative of the patient's breathing efforts can be used toadapt the operation of the ventilator to the needs of the patient, e.g.to make the ventilator supply breathing gas to the patient in synchronywith and in proportion to the patient's own breathing efforts.

The LP signal can be used in any type of support ventilation mode tobetter adapt the ventilation provided by the ventilator to the patient'sown breathing efforts. For example, the LP signal may be used as controlsignal during pressure support ventilation or NAVA ventilation of apatient, instead or in addition to the control parameters normally usedin those modes of support ventilation.

To some extent the invention can also be said to provide a novel type ofmechanical ventilation support mode, which novel type of support modehas much in common with the conventional NAVA mode since this novel typeof support mode also provides neurally adjusted ventilatory assist tothe patient. However, while in conventional NAVA controlling theventilator based on the diaphragm EMG (EMG_(Dia)), i.e. EMG signalsrelated to the muscular activity of the diaphragm, the present inventionprovides the possibility of operating the ventilator in a support modein which it is controlled based on LP signals related to the muscularactivity of muscles in the laryngopharyngeal region. Conventional NAVAin which ventilation is controlled based on EMG_(Dia) will hereinafterbe referred to as diaphragmatic NAVA (NAVA_(Dia)), whereas the noveltype of neurally adjusted ventilatory assist that is controlled based onLP signals will be referred to as laryngopharyngeal NAVA (NAVA_(LP)).

In some embodiments of the present disclosure, both LP signals andEMG_(Dia) are used to control the ventilator. This ventilation mode willbe referred to as diaphragmatic/laryngopharyngeal NAVA (NAVA_(Dia/LP)).

The sensor arrangement of the invention is hence configured to registerat least one LP signal that is related to the muscular activity of atleast one muscle of the laryngopharyngeal region. Preferably, the sensorarrangement is configured to register at least one LP signal that isrelated to the muscular activity of at least one muscle in the laryngealregion, i.e. at least one laryngeal muscle. Even more preferably, thesensor arrangement is configured to register at least one LP signalindicative of the muscular activity of the thyroarytenoid muscle(hereinafter referred to as the TA muscle) and/or the cricothyroidmuscle (hereinafter referred to as the CT muscle). Most preferably, theregistered LP signal is indicative of the activity of the TA muscle.

Thus, the sensor arrangement may be configured to register at least onesignal, herein referred to as an LP signal, which at least one signal isrelated to muscular activity of the TA muscle and/or the CT musclecaused by a breathing-related bioelectric signal transmitted to saidmuscle(s) from the respiratory center of the patient's brain, and soindicative of the patient's desire to breathe.

In some embodiments, the sensor arrangement for registering the at leastone LP signal may be an optical sensor arrangement, such as a fiberopticbronchoscope, configured to register the LP signal based on the patencyof the glottic opening.

In other embodiments, the sensor arrangement for registering the atleast one LP signal may be a bioelectric sensor arrangement configuredto register LP signals in form of bioelectric signals originating frommuscles in the laryngopharyngeal region. For example, the sensorarrangement may be a bioelectric sensor arrangement configured toregister the laryngopharyngeal EMG (EMG_(LP)), i.e. EMG signals relatedto the muscular activity of muscles in the laryngopharyngeal region.

In some embodiments, said bioelectric sensor arrangement may beconfigured to register the LP signal non-invasively from outside thepatient. For example, it is contemplated that the sensor arrangement maycomprise a set of surface electrodes configured to be attached to theskin of the patient's neck, in particular to the area around the throatof the patient, in order to register the EMG_(LP) of the patient fromthe surface of the skin. Preferably, said set of surface electrodescomprises at least two surface electrodes for registering LP signals.Additionally, the set of surface electrodes may comprise a referenceelectrode for capturing a reference signal which may be used for noisesuppression by a signal processing unit supplied with the signalscaptured by the electrodes.

In other embodiments, however, said bioelectric sensor arrangement isconfigured to register the LP signal from within the patient. In apreferred embodiment, the bioelectric sensor arrangement comprises anesophageal catheter configured to be inserted into the esophagus of apatient who is to be mechanically ventilated by a ventilator. Theesophageal catheter may comprise at least one electrode, hereinafterreferred to as an LP electrode, configured to register EMG_(LP) signalsrelated to the muscular activity of muscles in the laryngopharyngealregion when the catheter is inserted into the esophagus of the patient.Thereby, the present disclosure presents a novel type of bioelectricsensor which is similar to a conventional NAVA catheter but differstherefrom at least in the location of the electrodes for picking up thebioelectric signals and/or the length of the catheter. This novel typeof esophageal catheter may hereinafter be referred to as a NAVA_(LP)catheter to distinguish it from a conventional NAVA catheter for pickingup EMG_(Dia) signals, which conventional catheter is hereinafterreferred to as a NAVA_(Dia) catheter.

In some embodiments, the esophageal catheter may further comprise atleast one electrode, hereinafter referred to as a diaphragm electrode,configured to register EMG_(Dia) signals related to the muscularactivity of the diaphragm of the patient when the catheter is insertedinto the esophagus. This makes the esophageal catheter a combinedNAVA_(LP) and NAVA_(Dia) catheter, hereinafter referred to as aNAVA_(Dia/LP) catheter, comprising both at least one LP electrode forregistering EMG_(LP) in the laryngopharyngeal region of the patient andat least one diaphragm electrode for registering EMG_(Dia) in thediaphragmatic region of the patient.

Furthermore, the NAVA_(Dia/LP) catheter may comprise at least onereference electrode which may be located between the at least one LPelectrode and the at least one diaphragm electrode, i.e. in between saidLP zone and said diaphragm zone. In one embodiment, the NAVA_(Dia/LP)catheter comprises an upper array of at least two LP electrodes, a lowerarray of at least two diaphragm electrodes, and at least one referenceelectrode located between said upper array of LP electrodes and saidlower array of diaphragm electrodes. In another embodiment, theNAVA_(Dia/LP) catheter comprises an upper array of five LP electrodes, alower array of four diaphragm electrodes, and one reference electrodelocated between said upper and lower electrode arrays. The use of two ormore electrodes of each type is advantageous in that any two adjacentelectrodes then form an electrode pair for registering signals fromwhich a differential signal representative of the EMG_(LP) or EMG_(Dia)signal can be derived.

Furthermore, the system typically comprises a signal processing unitconfigured to receive the LP signals from the sensor arrangement and toderive, from said signals, one or more processed signals which may beused in automatic control of the ventilator and/or displayed on saiddisplay unit in order to serve as decision support for an operator inmanual or partially manual control of the ventilator.

In embodiments wherein the sensor arrangement comprises a NAVA_(LP)catheter or a NAVA_(Dia/LP) catheter, said signal processing unit may beconfigured to receive the EMG_(LP) signals from the LP electrodes of thecatheter, and to derive from said EMG_(LP) signals a signalrepresentative of the electric activity of the muscles of thelaryngopharyngeal region. This signal will hereinafter be referred to asthe Elp signal and can be said to correspond to the Edi signal ofconventional NAVA (NAVA_(Dia)), which Edi signal is derived from theEMG_(Dia) signals and used as control signal during conventionalNAVA_(Dia) ventilation. In more detail, the signal processing unit istypically configured to receive raw signals from said LP electrodes,which raw signals comprise EMG_(LP) components and noise, extract theEMG_(LP) signals from said received raw signals, and derive the Elpsignal from said extracted EMG_(LP) signals.

It should thus be appreciated that in one embodiment of the presentdisclosure, the signal processing unit may be configured to derive anElp signal from LP signals comprising EMG_(LP) signals, registered bymeans of a bioelectric sensor, e.g. a NAVA_(LP) or NAVA_(Dia/LP)catheter, and to transmit the Elp signal to a control unit forcontrolling a ventilator based on said Elp signal and/or for causingdisplay of the Elp signal on a display unit. The module of the signalprocessing unit that is configured to derive the Elp signal from the LPsignals received from the sensor arrangement will hereinafter bereferred to as the EMG_(LP) module.

The EMG_(LP) module may in some embodiments form part of a signalprocessing unit especially adapted for use with a NAVA_(Dia/LP)catheter. In this case, said processing unit may further comprise anEMG_(Dia) module configured to receive EMG_(Dia) signals captured bymeans of the diaphragm electrodes of the NAVA_(Dia/LP) catheter, derivean Edi signal from said EMG_(Dia) signals, and to transmit the Edisignal to the control unit for controlling the ventilator based on boththe Edi signal and said Elp signal, and/or for causing display of boththe Edi signal and said Elp signal on said display unit, and/orinformation derived from both the Edi signal and the Elp signal. In moredetail, said EMG_(Dia) module, corresponding to the what is oftenreferred to as the Edi module in the field of conventional NAVA, isconfigured to receive raw signals from said diaphragm electrodes, whichraw signals comprise EMG_(Dia) components, noise and typically also ECGcomponents originating from the electrical activity of the patient'sheart, extract the EMG_(Dia) signals from said received raw signals, andderive the Edi signal from said extracted EMG_(Dia) signals.

The signal processing unit may further comprise another module,hereinafter referred to as the comparator, configured to compare the Elpsignal with the Edi signal. The at least one control unit of the systemmay be configured to control the operation of the ventilation and/or tocause display of information on said at least one display unit based onthe result of said comparison.

In embodiments in which the operation of the ventilator is controlledbased on the Edi signal, said comparator may be configured to comparethe Edi signal with the Elp signal to validate the reliability of theEdi signal, and to cause the ventilator to switch from the currentEdi-controlled mode of operation to a ventilation mode not dependent onsaid Edi signal in case the reliability of the Edi signal cannot bevalidated.

Thus, according to one aspect of the present disclosure, there isprovided a system providing for an enhanced mode of NAVA ventilation inwhich at least one LP signal related to muscular activity of at leastone muscle in the laryngopharyngeal region of the patient is used tovalidate the accuracy of the Edi signal controlling the operation of theNAVA ventilator, and to prevent that the ventilator is controlled basedon inaccurate readings of said Edi signal. This functionality is offeredin the enhanced mode of NAVA ventilation, NAVA_(Dia/LP), made availableby the system of the present disclosure.

Controlling mechanical ventilation of a patient based on registered LPsignals in accordance with the principles of the present disclosure maybe advantageous during both invasive and non-invasive ventilation (NIV).However, it is particularly advantageous during NIV since the activityof the laryngopharyngeal muscles does not affect invasive ventilation tothe same extent as NIV. During NIV, wherein the patient interface isconstituted by e.g. a face mask or a nasal prong, the breathing gassupplied by the ventilator passes the upper respiratory tract of thepatient, including the laryngopharyngeal region, and so the muscularactivity of the muscles therein greatly affects the result of the NIV.During invasive ventilation, however, wherein the patient interface isconstituted by e.g. a tracheal tube, the breathing gas supplied by theventilator bypasses the laryngopharyngeal region of the patient whichmakes invasive ventilation insensitive or at least less sensitive to themuscular activity in this area.

The difficulties of NIV and the impact on NIV of the muscle activity ofthe muscles in the upper respiratory tract, including thelaryngopharyngeal region, are discussed in the article “Noninvasiveventilation and the upper airway: should we pay more attention?,”Oppersma et al, Critical Care 2013, 17:245, and further in the article“Absence of inspiratory laryngeal constrictor muscle activity duringnasal neurally adjusted ventilatory assist in newborn lambs”, Hajd-Ahmedet al., Journal of Applied Physiology, 113:63-70, 2012.

Since the LP signals registered by the sensor arrangement of the presentinvention carries information on the muscular activity in thelaryngopharyngeal region, the present invention provides for improvedNIV ventilation since this information can be used automatically ormanually to adapt the NIV ventilation to compensate for said muscularactivity.

Consequently, according to one embodiment of the present disclosure,there is provided a system for use in connection with mechanicalnon-invasive ventilation of a patient, provided by a ventilatorconnected to a patient by means of a non-invasive patient connector,such as a face mask or a nasal prong. The system comprises at least asensor arrangement and a control unit devised and configured as setforth above. The at least one control unit may further be configured toautomatically adjust the operation of the ventilator based on the atleast one registered LP signal to compensate for the influence ofmuscular activity in the laryngopharyngeal region on the NIVventilation, as indicated by said at least one LP signal.

As previously discussed, the LP signals registered by the sensorarrangement of the invention may be used to control the operation of theventilator in different ways in different modes of support ventilation.

In one embodiment, the at least one control unit of the system isconfigured to use the at least one registered LP signal in thedetermination of when to switch from one respiratory phase of theventilator to another, i.e. from ventilator inspiration to ventilatorexpiration or vice versa. In particular, the control unit may beconfigured to use the at least one LP signal in the determination ofwhen to initiate the inspiratory/expiratory (IE) phase transition,sometimes referred to as the inspiratory off-switch (IOS) or theinspiratory cycle-off (ICO), i.e. to determine the point in time atwhich the ventilator should switch from inspiration to expiration. Thelaryngopharyngeal muscle activity is generally low (the upper airway isopen) during desired inspiration of the patient in order for breathinggas to flow freely through the upper airway and onto the lungs of thepatient. The low level of muscle activity in the laryngopharyngealregion results in a weak LP signal during desired inspiration of thepatient. When the patient wishes to stop inspiration and startexpiration, the muscle activity in the laryngopharyngeal regionincreases (the upper airways are temporarily closed), resulting in asudden increase in the registered LP signal. The control unit may beconfigured to use this increase in LP signal amplitude to determine thepoint in time at which the ventilator should initiate the ICO, e.g. bydetermining when the LP signal exceeds a predetermined threshold valueserving as an LP signal trigger level for initiation of ICO.

Using the LP signal to determine when to initiate ICO may beadvantageous in any supported mode of ventilation, including but notlimited to conventional NAVA (NAVA_(Dia)), pressure support (PSV), andvolume support (VSV). The control unit may be configured to determinewhen to initiate ICO based on the at least one LP signal alone or basedon a combination of the at least one LP signal and one or more otherindicators of the patient's desire to initiate ICO.

For example, in NAVA modes or neurally triggered pneumatic modes inwhich the Edi signal is available, the control unit may be configured todetermine when to initiate ICO based on a comparison between the LPsignal and the Edi signal. This may provide for more robust control ofICO. Contrary to the LP signal, the Edi signal becomes weaker when thepatient wishes to stop inspiration and start expiration. In oneembodiment the control unit may be configured to determine when theamplitude of the Edi signal falls below a predetermined threshold valueserving as an Edi signal trigger level for initiation of ICO. Thecontrol unit may for example be configured to initiate ICO when, andonly when, the LP signal and the Edi signal have reached theirrespective trigger levels for initiation of ICO. The control unit maythus be configured to prevent initiation of ICO based on said Edi signalas long as the amplitude of the LP signal falls below a predeterminedvalue, thereby preventing false trigging of ICO.

Instead or in addition to the Edi signal, measured pressure and/or flowvalues indicative of the patient's desire to stop inspiration and startexpiration can be used in combination with the LP signal for more robustcontrol of ICO. For example, as well known in the art, flow and/orpressure in the inspiratory line of the ventilator or patient circuitconnecting the ventilator and the patient may be used as an indicator ofthe patient's desire to switch from inspiration to expiration. Thecontrol unit may be configured to use a signal indicative of said flowand/or pressure together with the LP signal in the determination of whento initiate ICO. In particular in the pressure support mode ofventilation (PSV), the lack of a robust criterion for initiation of ICOis a well-recognized problem. Monitoring and using an LP signal relatingto the laryngopharyngeal muscle activity in the determination of when toinitiate ICO may hence serve to solve or at least mitigate this problem.

Furthermore, the at least one control unit of the system may beconfigured to use the at least one registered LP signal to automaticallyadjust the level of ventilatory assist provided to the patient by theventilator, and/or to signal that the level of ventilatory assist shouldbe adjusted to an operator of the ventilator. A strong LP signal duringventilator inspiration typically indicates that the muscles of thelaryngopharyngeal region strive to decrease the flow of breathing gasflowing into the lungs of the patient, and so that the level ofventilatory assist (i.e. the flow and/or pressure of breathing gasprovided to the patient) is currently too high. The control unit may beconfigured to determine whether the level of ventilatory assist shouldbe adjusted based on the inspiratory LP signal, i.e. the LP signalregistered during ventilator inspiration. For example, the control unitmay be configured to compare the inspiratory LP signal with a thresholdvalue and, if the threshold value is exceeded, to automatically adjustthe level of ventilatory assist and/or to signal that the level ofventilatory assist should be adjusted to an operator of the ventilator,e.g. by generating a visual and/or audible alarm.

However, that the LP signal is strong during ventilator inspiration doesnot necessarily imply that the assist level is too high. That the LPsignal is strong may also be due to a mismatch or asynchrony between therespiratory phases of the ventilator and the respiratory phases of thepatient. Therefore, the control unit is preferably configured todetermine, based on the LP signal, whether there is synchrony orasynchrony between the respiratory phases of the ventilator and therespiratory phases of the patient, and to automatically adjust the levelof ventilatory assist and/or to signal that the level of ventilatoryassist should be adjusted only in case of synchrony between said phases.In ventilation modes in which the timing of transitions betweeninspiration and expiration phases are controlled based on an Edi signalcaptured from the patient, synchrony/asynchrony between the respiratoryphases of the ventilator and respiratory phases of the patient can bedetermined by the control unit by determining the synchrony/asynchronybetween the Edi signal and the LP signal. Thus, to distinguish thesituation of too high assist level (in which case the assist levelshould be decreased) from the situation of asynchrony between therespiratory phases of the ventilator and the patient, the control unitmay be configured to compare the LP signal and the Edi signal.Consequently, in embodiments where the Edi signal of the patient isavailable, the control unit may be configured to determine whether theventilatory assist level should be adjusted based on a comparisonbetween the Edi signal and the LP signal.

If it is determined that the level of ventilatory assist needs to beadjusted, the control unit may be configured to automatically determinean appropriate level of ventilatory assist by causing the ventilator toswitch between different levels of ventilatory assist, e.g. every fifthbreath, and to determine the appropriate level of ventilatory assistbased on a change in the registered LP signal between the differentlevels of ventilatory assist. For example, the control unit may beconfigured to determine the appropriate level of ventilatory assistthrough a titration process during which the control unit causes astepwise decrease in ventilatory assist level and determines theappropriate level of ventilatory assist as the upper level of two levelsbetween which the change in amplitude of the registered LP signal isless than a predetermined threshold value, and preferably nearly zero.Thus, the control unit may be configured to determine an appropriatelevel of ventilatory assist based on the LP signal response to at leastone change in ventilatory assist level.

Furthermore, the at least one control unit of the system may beconfigured to use the at least one registered LP signal to automaticallyadjust a level of positive end-expiratory pressure (PEEP) applied to thepatient, and/or to signal that the level of PEEP should be adjusted toan operator of the ventilator. A strong LP signal during ventilatorexpiration typically indicates that the muscles of the laryngopharyngealregion strive to maintain the pressure within the lungs by quenching theexpiration flow of gas out of the upper airway, which in turn may betaken as an indication of a need for increased PEEP. Thus, the controlunit may be configured to determine whether the current PEEP levelshould be adjusted based on the expiratory LP signal, i.e. the LP signalregistered during ventilation expiration. For example, the control unitmay be configured to compare the expiratory LP signal with a thresholdvalue and, if the threshold value is exceeded, to automatically adjustthe PEEP level and/or to signal that the PEEP level should be adjustedto an operator of the ventilator, e.g. by generating a visual and/oraudible alarm.

However, that the LP signal is strong during ventilator expiration doesnot necessarily imply that the PEEP level is too low. In accordance withthe above reasoning with regard to the relation between the LP signaland the level of ventilatory assist, the fact that the LP signal isstrong may also be due to a mismatch or asynchrony between therespiratory phases of the ventilator and the breathing efforts ofpatient. Therefore, the control unit is preferably configured todetermine whether there is synchrony or asynchrony between therespiratory phases of the ventilator and the respiratory phases of thepatient, and to automatically adjust the PEEP level and/or to signalthat the PEEP level should be adjusted only in case of synchrony betweensaid phases. The synchrony/asynchrony between the respiratory phases ofthe ventilator and respiratory phases of the patient may be determinedby the control unit based on a comparison between the Edi signal and theLP signal, as described above. Consequently, in one embodiment, thecontrol unit may be configured to determine whether the PEEP levelshould be adjusted based on a comparison between the Edi signal and theLP signal.

If it is determined that the PEEP level needs to be adjusted, thecontrol unit may be configured to automatically determine an appropriatelevel of PEEP by causing the ventilator to switch between different PEEPlevels, e.g. every fifth breath, and to determine the appropriate levelof PEEP based on a change in the registered LP signal between thedifferent PEEP levels. For example, the control unit may be configuredto determine the appropriate level of PEEP through a titration processduring which the control unit causes a stepwise increase in PEEP leveland determines the appropriate level of PEEP as the lower level of twolevels between which the change in amplitude of the registered LP signalis less than a predetermined threshold value, and preferably nearlyzero. Thus, the control unit may be configured to determine anappropriate PEEP level based on the LP signal response to at least onechange in PEEP level.

As discussed above, the at least one control unit of the system may beconfigured to use the at least one registered LP signal to detectventilator-patient asynchrony, i.e. asynchrony between the respiratoryphases of the ventilator and the desired respiratory phases of thepatient as indicated by detectable respiratory efforts. In a similarmanner, the control unit may be configured to detect false triggering ofrespiration phases, and in particular inspiration phases, inpatient-triggered ventilation modes. The LP signal may be used to detectboth pneumatic false-triggering, i.e. false-triggering based on measuredpressure and/or flow, and neural false-triggering, i.e. false-triggeringbased on a measured neural signal, such as the Edi signal. Thus, the LPsignal may be advantageously used by the control unit in detection offalse-triggering in both pneumatically controlled support modes, such aspressure support (PSV) and volume support (VSV), and in neurallycontrolled modes, such as NAVA. False-triggering is a well-recognizedproblem within the field of mechanical ventilation, in particular duringNIV ventilation (due to leakage in the patient interface), andfalse-triggered breaths are difficult to detect by means of the sensorsnormally included in ventilation systems according to prior art. The LPsignal detected by the sensor arrangement of the present disclosurehence offers a longed-for possibility of detecting false-triggering in areliable manner.

Furthermore, the control unit of the system may be configured to use theat least one registered LP signal to detect reverse phase respiration,i.e. a situation in which the respiratory phases of the ventilator andthe patient are reversed in relation to each other. Reverse phaserespiration is a problem mainly during ventilation in NAVA mode.

The control unit is preferably configured to detect false-triggeringand/or reverse phase respiration based on the inspiratory LP signal. Ifthe level of ventilatory assist is appropriate, a strong inspiratory LPsignal (the LP signal registered during ventilation inspiration) mayindicate that ventilator inspiration is initiated during patientexpiration, causing activation of the laryngopharyngeal muscles of thepatient to obstruct the undesired flow of inspiration gas received fromthe ventilator. In patient-triggered support modes of ventilation,initiation of ventilator inspiration during patient expiration can onlybe caused by false-triggering (in pneumatic support modes or NAVA) orreverse phase respiration (in NAVA). Thus, the control unit may beconfigured to detect false-triggering and/or reverse phase respirationbased on the LP signal by comparing the inspiratory LP signal with athreshold value, whereby false-triggering and/or reverse phaserespiration is detected in case said threshold value is exceeded. Incase of detection of false-triggering and/or reverse phase respiration,the control unit may be configured to automatically adjust the operationof the ventilator to avoid or at least mitigate the risk offalse-triggering and/or reverse phase respiration, and/or to generate analarm notifying the ventilator operator of the detected false-triggeringand/or reverse phase respiration, e.g. in form of a visual alarmdisplayed on a display unit.

That the level of ventilatory assist is appropriate, and thus that thestrong inspiratory LP signal is not caused by a too high level ofventilatory assist, may be determined by the control unit in differentways. For example, the control unit may be configured to use the abovedescribed titration process for automatic determination or verificationof the appropriate level of ventilatory assist. Furthermore, in pressuresupport mode, a sudden change in the inspiratory LP signal, especiallyduring short breaths, may indicate that the ventilatory assist level isappropriate and that said short breaths are false-triggered. The controlunit may be configured to use the level of the inspiratory LP signalduring such short and false-triggered breaths to determine or adjust theabove-mentioned threshold value with which the inspiratory LP signal maybe compared in order to detect false-triggering and/or reverse phaserespiration. Yet further, if the Edi signal is monitored in pressuresupport mode, the control unit may determine whether the level ofventilatory assist provided to the patient is appropriate by comparingthe ventilator settings and/or measured pressure and/or flow values withthe registered Edi signal. How to verify that the level of ventilatoryassist is suitably adjusted to the needs of the patient as manifested bythe Edi signal is well known in the art of NAVA. In NAVA, it is assumedthat ventilatory assist is provided in synchrony with and proportion tothe patient's own breathing, and so it must be assumed that a suddenincrease in the inspiratory LP signal is caused by false-triggering orreverse phase respiration.

A problem associated with conventional NAVA ventilation (NAVA_(Dia)),however, is false detection of reverse phase respiration. If theesophageal catheter is inserted too far into the esophagus of thepatient, the diaphragm electrodes may register bioelectric signals fromthe abdominal muscles instead of the diaphragm. The abdominal muscleswork in reverse phase in relation to the diaphragm, and controlling theventilator based on bioelectric signals from the abdominal muscles mayhence cause reverse phase respiration. NAVA ventilators of today containalgorithms for detecting such a faulty condition, and to switchventilation mode from NAVA to pressure support (NAVA (PS)) in case ofdetection of reverse phase respiration. However, said algorithms are notvery robust and false detection of reverser phase respiration is rathercommon. Such false detections cause the ventilator to undesirably switchfrom NAVA mode to said pressure support mode. The system of the presentdisclosure offers a solution to this problem since the control unit ofthe system can be configured to prevent the ventilator from switchingfrom NAVA to pressure support mode unless analysis of the registered LPsignal verifies the alleged detection of reverse phase respiration.Thus, the at least one control unit may be configured to determine,during ongoing NAVA ventilation, whether to switch to anotherventilation mode not dependent on the Edi signal, such as a pressuresupport mode, based on the registered LP signal. In particular, thecontrol unit may be configured to verify, based on the registered LPsignal, an alleged detection of reverse phase respiration, and toprevent the ventilator from switching from the NAVA mode to another modeof ventilation unless reverse flow ventilation can be verified. Sincethe LP signal, like the Edi signal, is indicative of the patient'sbreathing efforts and so the desired respiratory pattern of the patient,the control unit may verify or contest the alleged situation of reverseflow respiration by studying the LP signal during ventilator inspirationand/or expiration (i.e. the inspiratory and/or expiratory LP signal). Ifthe LP signal looks normal, i.e. the way it looks like when ventilatorrespiration and patient respiration are synchronized and in phase witheach other, the alleged detection of the reverser phase respiration canbe ignored and the ventilator can remain in the NAVA mode ofventilation.

According to another aspect of the present disclosure, there is provideda computer program which, when executed by the at least one control unitof the system, causes the operation of the ventilator to be based on theat least one registered LP signal, and/or causes display of informationrelated to said at least one LP signal on said display unit formonitoring the patient and/or the operation of the ventilator.

The computer program comprises computer-readable instructions, e.g. inform of program code, which for example may be stored in a non-volatilememory of said at least one control unit. When executed by the controlunit, e.g. by means of at least one processor of the control unit, thecomputer-readable instructions causes the control unit to perform, or tocause other system components to perform, the above described stepsrelated to use of the at least one LP signal registered by the sensorarrangement.

More advantageous aspects and effects of the method as well as the gasdelivery system and the additive gas delivery apparatus of the inventionwill be described in the detailed description following hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a system for use in connection with mechanicalventilation of a patient, according to an exemplary embodiment of theinvention.

FIG. 2 illustrates the respiratory tract of a human being.

FIG. 3A is a posterior view of the larynx of a human being showingcertain muscles in the laryngopharyngeal region.

FIG. 3B is a top view showing some intrinsic muscles of the larynx of ahuman being, including the thyroarytenoid and cricothyroid muscles.

FIG. 4A illustrates the electrical activity of the thyroarytenoidmuscle, the cricothyroid muscle, and the diaphragm of a patientundergoing NIV ventilation without continuous positive airway pressure.

FIG. 4B illustrates the electrical activity of the thyroarytenoidmuscle, the cricothyroid muscle, and the diaphragm of a patientundergoing NIV ventilation with pressure support.

FIG. 5 illustrates a bioelectric sensor arrangement according to anexemplary embodiment of the invention.

FIG. 6 illustrates the bioelectric sensor arrangement of FIG. 5 wheninserted into the esophagus of a patient.

FIG. 7 illustrates a signal processing unit according to an exemplaryembodiment of the invention, adapted for use with the bioelectric sensorarrangement of FIGS. 5 and 6.

FIG. 8 illustrates a system for use in connection with mechanicalventilation of a patient, according to another exemplary embodiment ofthe invention.

FIG. 9 illustrates a bioelectric sensor arrangement according to anotherexemplary embodiment of the invention.

FIG. 10 is a flowchart illustrating a method for determining when duringventilator inspiration to initiate inspiratory cycle-off (ICO),according to an exemplary embodiment of the invention.

FIG. 11 is a flowchart illustrating a method for determining if a levelof ventilatory assist currently provided to a patient by a ventilatorshould be adjusted, according to an exemplary embodiment of theinvention.

FIG. 12 is a flowchart illustrating a method for determining if a levelof PEEP currently applied to a patient by a ventilator should beadjusted, according to an exemplary embodiment of the invention.

FIG. 13 is a flowchart illustrating a method for detecting falsetriggering of respiration phases in patient-triggered ventilation modes,and/or reverse phase respiration, according to an exemplary embodimentof the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 illustrates a system 1 for use in connection with mechanicalventilation of a patient 3, provided by a ventilator 5. The systemcomprises at least a sensor arrangement 7 configured to register atleast one signal, S_(LP), related to muscular activity of at least onemuscle in the laryngopharyngeal region 9 of the patient 3. Such a signalis herein referred to as a laryngopharyngeal signal (LP signal).Further, the system 1 comprises at least one control unit 11 configuredto control the operation of said ventilator 5 based on the at least oneregistered LP signal, and/or to cause display of information related tosaid at least one registered LP signal on at least one display unit 13A,13B.

The at least one display unit 13A, 13B may be a display unit 13A of theventilator 5 and/or a display unit 13B of a stand-alone monitoringsystem 15 for monitoring the status of the patient 3 and/or theoperation of the ventilator 5.

That the operation of the ventilator 5 is controlled based on theregistered LP signal means that the ventilator 5 is controlled based onthe signal, SLP, captured by the sensor arrangement 7, or a signal,S1(SLP), derived therefrom, which signal is dependent on the signal,SLP, captured by the sensor arrangement 7. Likewise, that informationrelated to the registered LP signal is displayed on a display unit 13A,13B means that the at least one captured signal itself, SLP, isdisplayed on the display unit, or that a signal, S2(SLP), or any otherinformation derived from the captured signal is displayed on saiddisplay unit 13A, 13B.

In FIG. 1, the at least one control unit 11 is illustrated as a separateunit. However, it should be appreciated that the at least one controlunit 11 of the present invention may be integrated in the ventilator 5and/or the monitoring system 15. For example, the sensor arrangement 7may be connected directly to the ventilator 5 in order for an internalcontrol unit of the ventilator 5 to use the registered LP signal ascontrol signal for controlling the operation of the ventilator, and/orfor causing display of information related thereto on the display unit13A of the ventilator 5. The sensor arrangement 7 may also be directlyconnected to the monitoring system 15 in order for an internal controlunit of the monitoring system to cause display of information related tothe registered LP signal on the display unit 13B of the monitoringsystem 15.

FIG. 2 illustrates the respiratory tract of a human being. Therespiratory tract comprises an upper respiratory tract 10. The upperrespiratory tract 10 includes the laryngopharyngeal region 9 from whichthe LP signal originates. The laryngopharyngeal region 9 forms a lowerpart of the upper respiratory tract 10. The upper respiratory tract 10includes the nasal cavity, the pharynx, and the larynx. Thelaryngopharyngeal region 9 includes the pharynx and the larynx but notthe nasal cavity, which is located above the laryngopharyngeal region.

Furthermore, the respiratory tract comprises a lower respiratory tract12. The lower respiratory tract 12 includes the trachea and the lungs.The diaphragm, the major dome-shaped muscle of respiration, is locatedbelow the lungs and separates the thoracic cavity containing the heartand the lungs from the abdominal cavity. The region of the diaphragm 18may herein be referred to as the diaphragmatic region.

Also shown in FIG. 2 is the esophagus, running alongside parts of therespiratory tract, including the laryngeal region of the upperrespiratory tract 10.

FIG. 3A is a posterior view of the larynx 16 showing certain muscles inthe laryngopharyngeal region 9. Of particular interest for the presentinvention is the glottal constrictor, namely the thyroarytenoid (TA)muscle 17, and the glottal dilator, namely the cricothyroid (CT) muscle19. The epiglottis 21, the thyroid cartilage 23 and the first trachealring 25 are also indicated in the drawing for the purpose oforientation.

FIG. 3B is a top view showing some intrinsic muscles of the larynx 16,including said thyroarytenoid muscle 17 and said cricothyroid muscle 19.For the purpose of orientation, the thyroid cartilage 23, the lateralcricoarytenoid muscle 27 and the posterior cricoarytenoid muscle havealso been indicated in the drawing.

FIGS. 4A and 4B each show three graphs illustrating the electricalactivities of different muscles during NIV ventilation. FIG. 4Aillustrates electrical muscle activity during NIV without continuouspositive airway pressure (CPAP), and FIG. 4B illustrates electricalmuscle activity during NIV with pressure support ventilation.

In each of FIGS. 4A and 4B, the upper graph illustrates a signal curve,SLP(TA), representing the electrical activity of the thyroarytenoidmuscle 17, the middle graph illustrates a signal curve, SLP(CT),representing the electrical activity of the cricothyroid muscle 19, andthe lower graph illustrates a signal curve, Edi, representing theelectrical activity of the diaphragm. The vertical dashed lines indicatea ventilator inspiration phase (insp) and a ventilator expiration phase(exp) of the NIV ventilation. The signals SLP(TA) and SLP(CT) relatingto the muscular activity of the TA and CT muscles, respectively, areexamples of what is herein referred to as LP signals.

During spontaneous breathing, both the thyroarytenoid muscle 17 andcricothyroid muscles 19 are active—thyroarytenoid muscle activityoccurring primarily at the end of inspiration. However, with applicationof pressure support ventilation, in particular during NIV, inspiratorycricothyroid activity disappears whereas activity of the thyroarytenoidmuscle increases. This results in glottal narrowing and restrictedventilation, as seen in FIG. 4A.

In contrast to pressure support, glottal constrictor muscle activity(i.e. TA activity) does not increase with NAVA since NAVA induces lessglottal closure and more synchronous ventilation. A possible underlyingmechanism for the absence of glottal constrictor activity duringinspiration with NAVA is that the pressure rise mimics the normalprogressive recruitment of the diaphragmatic motor units, whereas duringPSV, insufflation from the ventilator is performed with a constant levelof pressure (decelerating flow pattern), often with a short inspiratoryrise time to further decrease the patient's inspiratory work.

With reference now made to all previous drawings, the at least one LPsignal, SLP, registered by the sensor arrangement 7 and used inaccordance with the principles of the present invention, is related tomuscular activity of at least one muscle in the laryngopharyngeal region9 of the patient 3. Preferably, said at least one LP signal relates tothe muscular activity of at least one laryngeal muscle, and even morepreferably to the muscular activity of the TA muscle 17 and/or the CTmuscle 19. Thus, the signals denoted SLP(TA) and SLP(CT) in FIGS. 4A and4B, originating from the muscle activities of the TA and CT muscles,respectively, may, in some embodiments, constitute said LP signal.

The sensor arrangement 7 for measuring the at least one LP signal maycomprise an optical sensor, such as a fiberoptic bronchoscope, forregistering information indicative of the patency of the glotticaperture, and processing means configured to process the informationregistered by the optical sensor and generate an LP signal indicative ofsaid patency and thus of the muscular activity of the laryngeal musclesand in particular the muscular activity of the TA and CT muscles. Forexample, said processing means may be configured to generate an LPsignal the amplitude of which is proportional to the patency of theglottic opening. In some embodiments the optic sensor may be configuredto capture images of the glottic opening, whereby said processing meansmay comprise image processing means for determining the patency, ordegree of opening, of the glottic opening based on the captured images.

In a preferred embodiment, however, the sensor arrangement 7 forregistering the at least one LP signal may be a bioelectric sensorarrangement configured to register LP signals in form of bioelectricsignals originating from muscles in the laryngopharyngeal region 9.

FIG. 5 illustrates an exemplary embodiment of such a bioelectric sensorarrangement 7A. The bioelectric sensor arrangement 7A comprises anesophageal catheter 31 configured to be inserted into the esophagus ofthe patient 3. The esophageal catheter 31 comprises a plurality ofelectrodes e1-e5, herein referred to as laryngopharyngeal (LP)electrodes, located in an upper zone 33 in an upper part of the catheter31. The LP electrodes e1-e5 are configured to register LP signals inform of EMG signals related to the muscular activity of at least onemuscle in the laryngopharyngeal region 9, such as the TA and/or the CTmuscle of the larynx 16. Such EMG signals related to laryngopharyngealmuscle activity are herein referred to as EMGLP signals.

The esophageal catheter 31 further comprises a plurality of diaphragmelectrodes e6-e9, located in a lower zone 35 in a lower part of thecatheter 31. The diaphragm electrodes e6-e9 are configured to registerbioelectric signals in form of EMG signals related to the muscularactivity of the diaphragm, which EMG signals are herein referred to asEMGDia signals.

The esophageal catheter 31 further comprises a reference electrode, e0,positioned in between said upper zone of LP electrodes and said lowerzone of diaphragm electrodes.

Potential signals Se0-9, indicative of the potentials of the electrodese0-e9 are transmitted from the electrodes e0-e9 towards a signalprocessing module (not shown) along electrode wires which are bundledtogether to form a single signal cable 37 proximate the catheter 31. Ina more distal end, the electrode wires W1-10 are separated to allowconnection of each electrode wire to a respective input of said signalprocessing unit.

The potential signals Se1-9 are indicative of the potentials of theelectrodes e1-e9 in relation to the reference electrode e0. Thesesignals Se1-9 are bioelectric raw signals comprising EMG componentsrelated to the activity of the laryngopharyngeal muscles and thediaphragmatic muscles. The bioelectric raw signals denoted Se1-5registered by the LP electrodes e1-e5 comprises EMGLP components andconstitute examples of what is herein referred to as the at least one LPsignal. The bioelectric raw signals denoted Se6-9 registered by thediaphragm electrodes e6-e9 comprises EMGDia components and correspond tothe bioelectric raw signals picked up by the electrodes of aconventional NAVA catheter.

The esophageal catheter 31 thus constitutes a novel type of NAVAcatheter comprising two different groups of electrodes, e1-e5 and e6-e9,for registering EMGLP and EMGDia signals, respectively, in order toallow the operation of a ventilator to be controlled based on themuscular activity in both the laryngopharyngeal region 9 and thediaphragmatic region 18. This novel type of NAVA catheter is hereinreferred to as NAVADia/LP catheter.

The upper zone 33 in which the LP electrodes e1-e5 are located isarranged on an upper half of the catheter 31, and the lower zone 35 inwhich the diaphragm electrodes e6-e9 are located is arranged on a lowerhalf of the catheter 31. With reference now also made to FIG. 6, thecatheter 31 and its upper 33 and lower 35 zones are dimensioned suchthat at least one LP electrode e1-e5, and preferably at least one LPelectrode pair constituted by two adjacent LP electrodes, is positionedin the laryngopharyngeal region 9, at or near the larynx 16 of thepatient 3, whereas at least one diaphragm electrode e6-e9, andpreferably at least one diaphragm electrode pair constituted by twoadjacent diaphragm electrodes, is positioned in the diaphragmatic region18, at or near the diaphragm of the patient 3, when the esophagealcatheter 31 is inserted into the esophagus of the patient.

The LP electrodes of the upper zone 33 are distributed along the lengthof said upper zone in the longitudinal direction of the catheter 31.Likewise, the diaphragm electrodes of the lower zone 35 are distributedalong the length of the lower zone in the longitudinal direction of thecatheter 31.

Preferably, the upper 33 and lower 35 zones of the catheter is separatedby a distance of at least 5 cm, meaning that the vertical distance alongthe catheter, between the bottom LP electrode e5 and the top diaphragmelectrode e6 is at least 5 cm. The length of the catheter 31 and thelengths of the upper 33 and lower zones 35 may be tailored to theanatomy of the patient 3.

FIG. 7 illustrates an exemplary embodiment of a signal processing unit39 adapted for use with the NAVADia/LP catheter 31 in FIG. 5. The signalprocessing unit 39 is configured to receive and process the raw signalsSe1-5 registered by the sensor arrangement 7A, and to transmit one ormore signals derived from said raw signals Se1-5 to the at least onecontrol unit 11 of the system, e.g. to be used as control signals in thecontrol of the ventilator 5 (see FIG. 1).

The signal processing unit 39 comprises a module 41A, herein referred toas an EMGLP module, for receiving and processing the bioelectric rawsignals Se1-5 registered by the LP electrodes e1-e5. The EMGLP module41A is configured to process the raw signals Se1-5 in various ways, e.g.by reducing noise, in order to extract the EMGLP components. Theextracted EMGLP signals are then further processed by the EMGLP module41A to derive a signal reflecting the electrical activity of the atleast one muscle of the laryngopharyngeal region, such as the TA muscle17 or the CT muscle 19. This signal is herein referred to as the Elpsignal, which signal can be said to correspond to the Edi signal ofconventional NAVA (NAVADia).

The signal processing unit 39 further comprises a module 43, hereinreferred to as an EMGDia module, for receiving and processing thebioelectric raw signals Se6-9 registered by the diaphragm electrodese6-e9. The EMGDia module 43 is configured to process the raw signalsSe6-9 in various ways, e.g. by reducing noise and filtering out ECGcomponents also comprised in the raw signals, in order to extract theEMGDia components from the raw signals. The extracted EMGDia signals arethen further processed by the EMGDia module 43 to derive a signalreflecting the electrical activity of the diaphragm. This signal is theEdi signal commonly used to control the operation of ventilatorsoperation in conventional NAVA mode (NAVADia).

As illustrated in the drawing, the EMGLP module 41A and the EMGDiamodule 43 further comprise a respective input for receiving thepotential signal Se0 from the reference electrode e0. This signal may beused as reference signal by each of said modules 41A, 43 in thedetermination of the EMGLP and the EMGDia components, respectively, in amanner well-known in the art of electromyography.

The signal processing module 39 may further comprise a module, hereinreferred to as the comparator 45, configured to compare the Elp signalwith the Edi signal. The at least one control unit of the system 11 maybe configured to control the operation of the ventilation and/or tocause display of information on said at least one display unit 13A, 13Bbased on the result of said comparison. In this exemplary embodiment,the comparator 45 is configured to generate, based on said comparison, areliability signal □S indicative of the reliability of any or both ofsaid Elp and Edi signals. The comparator may for example be configuredto generate said reliability signal based on the amplitudes of the Elpand Edi signals. It may also be configured to generate said reliabilitysignal based on the synchrony/asynchrony of the Elp and Edi signals. Thecontrol unit 11 may be configured to generate an alarm if saidreliability signal □S indicates that any or both of said Elp and Edisignals are currently unreliable. The alarm may be a visual and/or anaudible alarm, e.g. a visual alarm displayed on a display unit 13A ofthe ventilator or the display unit 13B of the monitoring system 15. Forexample, if the reliability signal □S indicates asynchrony between theElp signal and the Edi signal, which in turn indicates asynchronybetween the muscular activities of the laryngopharyngeal muscles and themuscular activity of the diaphragm or faulty detection or processing ofthe signals from which the Elp and Edi signals are derived, an alarmsignal may be generated notifying the ventilator operator that one orboth of the Elp and Edi signals are probably unsuitable for use as acontrol signal for controlling the operation of the ventilator. Asdiscussed above, asynchrony between the Elp signal and the Edi signalmay also be due to the fact that the level of ventilatory assistprovided by the ventilator is not optimal, or that the current PEEPlevel is not optimal.

In embodiments in which the operation of the ventilator 5 is controlledbased on the Edi signal, said comparator 45 may be configured to comparethe Edi signal with the Elp signal to validate the reliability of theEdi signal. The control unit 11 may be configured to cause interruptionof the Edi-controlled NAVA ventilation in case the comparison indicatesthat the Edi signal is unreliable. For example, in case the comparisonshows that the Edi signal is unreliable, the control unit 11 may beconfigured to cause the ventilator 5 to switch from the currentEdi-controlled mode of operation to a ventilation mode not dependent onsaid Edi signal, e.g. to a pneumatic support mode, such as a pressuresupport or volume support mode.

The signal processing module 39 may further comprise a module,hereinafter referred to as the combiner 47, configured to combine theElp signal and the Edi signal into a combined signal Scomb based on bothsaid Elp signal and said Edi signal. This combined signal Scomb may beused in addition or instead of the Elp and/or the Edi signal as acontrol signal for controlling the operation of the ventilator.

The signals Elp, □S and Scomb are all examples of signals derived fromLP signals related to laryngopharyngeal muscle activity, which signalsmay be used in accordance with the principles of the present inventionto provide improved neural control of a ventilator 5 providing supportventilation to a patient 3.

FIG. 8 illustrates another exemplary embodiment of a system 1A accordingto the present disclosure. The system 1A is seen to comprise a sensorarrangement 7A as described above with reference to FIG. 5, a signalprocessing unit 39 as described above with reference to FIG. 7, aventilator 5 providing support ventilation to a patient 3, and amonitoring system 15 for monitoring patient and ventilator parameters.The signal processing unit 39 is coupled to an internal control unit 11Aof the ventilator 5, configured to control the operation of theventilator based on the Edi signal derived from the EMGDia signals, i.e.to operate the ventilator in a conventional NAVA mode. To this end, thecontrol unit 11A is configured to transmit control signals to a gasregulating unit 48 of the ventilator 5 in dependence of the Edi signal.

The signal processing unit 39 is also coupled to an internal controlunit 11B of the monitoring system 15, configured to cause display ofsignals and/or information contained in the signals received from thesignal processing unit 39, and derived from the bioelectric signalsSe1-9 captured by the sensor arrangement 7A. The display unit 13B of themonitoring system is seen to comprise a first display window 49 showinga first signal curve 51 representing the Edi signal, and a second signalcurve 53 representing a the proximal patient pressure, i.e. a pressuresubstantially corresponding to the airway pressure of the patient 3,which pressure may be measured by means of a pressure sensor of theventilator 5 and communicated to the monitoring system 15 via acommunication connection 55. The display unit 13B further comprises asecond display window 57 showing said Edi signal curve 51 together witha second signal curve 59 representing the Elp signal derived from thesignals Se1-5 and related to the laryngopharyngeal muscle activity ofthe patient 3. The Edi signal curve 51 and the Elp signal curve 59 areassociatively displayed in a common display window 57 in order for anoperator of the ventilator 5 to easily compare the Edi signal and theElp signal. The monitoring system 15 is hence configured toassociatively display information related to the muscular activity ofthe diaphragm of the patient 3 and information related to the muscularactivity of at least one muscle in the laryngopharyngeal region of thepatient 3. The information is preferably displayed in a common frame ofreference in order to facilitate comparison between the informationcontents, e.g. by displaying the Edi and Elp signal curves in a commontime frame.

Although illustrated as a separate external unit in this exemplaryembodiment, it should be appreciated that the signal processing unit 39may also be integrated into the ventilator 5 or the monitoring system15. In this case, information derived by the signal processing unit 39could still be supplied to both the ventilator 5 and the monitoringsystem 15, e.g. by transmitting the information via the communicationconnection 55. In some embodiments, the signal processing unit 39 may beintegrated in the ventilator 5 to form a module intended to replace theEdi module of conventional NAVA-enabled ventilators, so as to adapt theventilator 5 for the enhanced NAVADia/LP functionality described herein.

FIG. 9 illustrates a bioelectric sensor arrangement 7B according toanother embodiment of the present disclosure.

This bioelectric sensor arrangement 7B comprises a set of surfaceelectrodes for registering the at least one LP signal non-invasivelyfrom outside the patient 3. In this exemplary embodiment, thebioelectric sensor arrangement 7B comprises two surface electrodes e11and e12 which are attached to the skin of the patient's neck, outsidethe laryngopharyngeal region 9 of the upper airways of the patient 3.Just like the LP electrodes e1-e5 of the esophageal catheter 31described above with reference to FIG. 5, the surface electrodes e11,e12 of the bioelectric sensor arrangement 7B are configured to registerpotential signals Se11, Se12 in form of bioelectric raw signals carryinginformation of the EMGLP of the patient 3, which signals henceconstitute another example of what is herein referred to as LP signals.For the sake of consistency in terminology, the electrodes e11 and e12serving to register said LP signals are hereinafter referred to as LPelectrodes of the bioelectric sensor arrangement 7B. The bioelectric rawsignals Se11, Se12 registered by the LP electrodes e11, e12 aretransmitted to an EMGLP module 41B similar to the EMGLP module 41A inFIG. 7.

Consequently, the EMGLP module 41B is configured to process the rawsignals Se11, Se12 in various ways, e.g. by reducing noise, in order toextract the EMGLP components of said raw signals. The extracted EMGLPsignals may then be further processed by the EMGLP module 41B to derivethe above mentioned Elp signal reflecting the electrical activity of theat least one muscle of the laryngopharyngeal region, such as the TAmuscle 17 or the CT muscle 19 (see FIGS. 3A and 3B).

The bioelectric sensor arrangement 7B is further seen to comprise areference electrode e00. The potential signal Se00 registered by thereference electrode e00 may also be transmitted to the EMGLP module 41Bin order to be used by said module as reference signal in thedetermination of the EMGLP components of the raw signals Se11, Se12, ina manner well-known in the art of electromyography.

With simultaneous reference to previous drawings, and in particularFIGS. 1 and 8, it should be appreciated that the EMGLP module 41B,although not illustrated in FIG. 9, is coupled to the at least onecontrol unit 11, 11A, 11B of the system 1, 1A of the present disclosurein order for said at least one control unit to control the operation ofthe ventilator 5 based on the LP signals Se11, Se12 registered by thebioelectric sensor arrangement 7B, and typically based on an Elp signalderived from said LP signals, and/or to cause display of informationrelated to said LP signals on at least one display unit 13A, 13B formonitoring the patient 3 and/or the operation of the ventilator 5, e.g.display of a signal curve representing said Elp signal.

Furthermore, it should be appreciated that the bioelectric sensorarrangement 7B for surface detection of LP signals may be advantageouslyused in combination with at least one other bioelectric sensorarrangement for detection of bioelectric signals representative of theEMGDia of the patient 3, such as a conventional NAVA catheter and/oranother set of surface electrodes positioned outside the diaphragmaticregion of the patient 3 and configured to register such bioelectricsignals from the surface of the patient's skin. In this case, the atleast one control unit 11, 11A, 11B of the system 1, 1A may beconfigured to control the operation of the ventilator 5 and/or to causedisplay information on said at least one display unit 13A, 13B based onboth the LP signals representative of the EMGLP of the patient 3,captured by the surface electrodes e11 and e12, and the bioelectricsignals representative of the EMGDia of the patient 3, in accordancewith any of the principles described above.

In this case, the EMGLP module 41B may form part of a signal processingunit (not shown) configured to derive an Elp signal from the signalsregistered by the LP surface electrodes e11, e12 of the bioelectricsensor arrangement 7B, which signal processing unit is furtherconfigured to derive an Edi signal from bioelectric signalsrepresentative of the EMGDia of the patient 3, captured by and receivedfrom said at least one other sensor arrangement. Thus, it should beappreciated that the EMGLP module 41B may form part of a signalprocessing unit similar to the signal processing unit 39 of FIG. 7, inwhich the EMGLP module 41A for determination of an Elp signal based onthe LP signals captured by the LP electrodes e1-e5 of the esophagealcatheter 31 is replaced by the EMGLP module 41B for determination of anElp signal based on the LP signals captured by the LP surface electrodese11, e12, and in which the EMGDia module 43 may or may not be replacedby another EMGDia module for determination of an Edi signal based onbioelectric signals representative of the EMGDia of the patient 3,captured by said at least one other sensor arrangement.

As previously discussed, the registered LP signals may be used toimprove mechanical ventilation in many different ways in different modesof ventilation. In the following, some exemplary methods of use of theat least one registered LP signal will be described with reference tovarious flow charts. Unless stated otherwise, the methods are carriedout by the at least one control unit 11 of the system 1 by executing acomputer program stored in a memory of said control unit 11 by means ofa processing unit, such as a microprocessor.

FIG. 10 is a flow chart illustrating a method for determining, based onthe at least one registered LP signal, when, during ventilatorinspiration, to initiate inspiratory cycle-off (ICO), i.e. when to causethe ventilator to switch from an inspiratory phase to an expiratoryphase.

In a first step, S101, at least one LP signal related to muscularactivity of at least one muscle in the laryngopharyngeal region of apatient undergoing ventilatory treatment is registered.

In a second step, S102, the at least one registered LP signal iscompared with a reference value and/or a reference signal. Saidreference value may be a threshold value serving as an LP signal triggerlevel for initiation of ICO, and said reference signal may be acurrently available Edi signal of the patient.

In a third step, S103, a point in time at which to initiate ICO, i.e. apoint in time at which to switch from ventilator inspiration toventilator expiration, is determined based on the result(s) of thecomparison(s) in step S102.

FIG. 11 is a flow chart illustrating a method for determining, based onthe at least one registered LP signal, if a level of ventilatory assistcurrently provided to a patient by a ventilator should be adjusted.

In a first step, S111, at least one LP signal related to muscularactivity of at least one muscle in the laryngopharyngeal region of thepatient is registered.

In a second step, S112, the at least one registered LP signal iscompared with a reference value and/or a reference signal. Saidreference value may be a threshold value indicating too high level ofventilatory assist, and said reference signal may be a currentlyavailable Edi signal of the patient. Preferably, the comparison is madeusing an inspiratory LP signal, i.e. an LP signal registered duringventilator inspiration.

In a third step, S113, it is determined whether the level of ventilatoryassist should be adjusted based on the result(s) of the comparison(s) instep S112.

If it is determined that the level of ventilatory assist should beadjusted, i.e. that the level of ventilatory assist currently providedto the patient is too high or too low, the method may comprise asubsequent step (not shown) in which the level of ventilatory assist isautomatically adjusted, and/or in which a signal indicating that thelevel of ventilatory assist should be adjusted is generated so as tonotify an operator of the ventilator thereof.

FIG. 12 is a flow chart illustrating a method for determining, based onthe at least one registered LP signal, if a level of PEEP currentlyapplied to a patient by a ventilator should be adjusted.

In a first step, S121, at least one LP signal related to muscularactivity of at least one muscle in the laryngopharyngeal region of thepatient is registered.

In a second step, S122, the at least one registered LP signal iscompared with a reference value and/or a reference signal. Saidreference value may be a threshold value indicating too low PEEP level,and said reference signal may be a currently available Edi signal of thepatient. Preferably, the comparison is made using an expiratory LPsignal, i.e. an LP signal registered during ventilator expiration.

In a third step, S123, it is determined whether the PEEP level should beadjusted based on the result(s) of the comparison(s) in step S122.

If it is determined that the PEEP level should be adjusted, i.e. thatthe PEEP currently applied to the patient is too high or too low, themethod may comprise a subsequent step (not shown) in which the PEEPlevel is automatically adjusted, and/or in which a signal indicatingthat the PEEP level should be adjusted is generated so as to notify anoperator of the ventilator thereof.

FIG. 13 is a flow chart illustrating a method for detecting, based onthe at least one registered LP signal, false triggering of respirationphases, in particular inspiration phases, in patient-triggeredventilation modes, and/or reverse phase respiration, i.e. a situation inwhich the respiratory phases of the ventilator and the patient arereversed in relation to each other.

In a first step, S131, at least one LP signal related to muscularactivity of at least one muscle in the laryngopharyngeal region of thepatient is registered.

In a second step, S132, the at least one registered LP signal iscompared with a reference value. For example, the comparison may be madebetween the inspiratory LP signal, i.e. a part of the LP signalregistered during ventilator inspiration, and a threshold value for saidinspiratory LP signal. If the inspiratory LP signal exceeds saidthreshold value it is an indication of false-triggering of theventilator inspiration phase and/or an indication of reverse phaserespiration of the ventilator and the patient, given that the level ofventilatory assist currently provided to the patient is not too high.

In a third step, S133, it is determined, based on the result of thecomparison in step S132, whether false-triggering and/or reverse phaserespiration seems to have occurred.

If it is determined in step 133 that false-triggering and/or reversephase respiration is likely to have occurred, the method may comprise asubsequent step (not shown) in which the operation of the ventilator isautomatically adjusted to avoid or at least mitigate the risk offalse-triggering and/or reverse phase respiration, and/or in which asignal indicating the detection of false-triggering and/or reverse phaserespiration is generated in order to notify an operator of theventilator thereof.

DEFINITIONS AND ABBREVIATIONS

-   EMG Electromyogram-   EMGLP EMG representative of laryngopharyngeal muscle activity-   EMGDia EMG representative of diaphragmatic muscle activity-   LP Laryngopharynx/laryngopharyngeal-   NAVA Neurally adjusted ventilatory assist-   NAVADia Diaphragmatic NAVA; Conventional NAVA wherein ventilation is    controlled based on signals related to the muscular activity of the    diaphragm-   NAVALP Laryngopharyngeal NAVA; Novel type of NAVA wherein    ventilation is controlled based on signals related to the muscular    activity of muscles in the laryngopharyngeal region-   NAVADia/LP Diaphragmatic/Laryngopharyngeal NAVA; Novel type of NAVA    wherein ventilation is controlled based on both signals related to    the muscular activity of the diaphragm and signals related to the    muscular activity of muscles in the laryngopharyngeal region-   NAVA(PS) Pressure support mode of NAVA-enabled ventilator-   PSV Pressure support mode-   VSV Volume support mode

Although modifications and changes may be suggested by those skilled inthe art, it is the intention of the Applicant to embody within thepatent warranted hereon all changes and modifications as reasonably andproperly come within the scope of the Applicant's contribution to theart.

1. A system for use in connection with mechanical ventilation of apatient, provided by a ventilator, the system comprising: a bioelectricsensor arrangement configured to register at least one laryngopharyngeal(LP) signal originating from and relating to muscular activity of atleast one muscle in the laryngopharyngeal region of said patient, and atleast one controller configured to control the operation of saidventilator based on said at least one LP signal, wherein the controlleris configured to: determine if a level of ventilatory assist currentlyprovided to the patient should be adjusted, based on said at least oneLP signal; or determine if a level of positive end-expiratory pressure(PEEP) currently applied to the patient should be adjusted, based onsaid at least one LP signal; or determine when to initiate aninspiratory cycle-off by determining when said at least one LP signalexceeds a certain threshold value serving as a trigger level for saidinspiratory cycle-off; or use said at least one LP signal to detectfalse-triggering of patient-triggered respiration phases and/or reversephase respiration.
 2. The system according to claim 1, wherein thecontroller is configured to determine if the level of ventilatory assistcurrently provided to the patient should be adjusted, based on said atleast one LP signal.
 3. The system according to claim 2, wherein said atleast one LP signal is an inspiratory LP signal registered duringventilator inspiration, the at least one controller is configured todetermine if the level of ventilatory assist currently provided to thepatient should be adjusted based on the inspiratory LP signal.
 4. Thesystem according to claim 3, wherein the at least one controller isconfigured to compare the inspiratory LP signal with a threshold valueand, if the threshold value is exceeded, to automatically adjust thelevel of ventilatory assist and/or to signal that the level ofventilatory assist should be adjusted to an operator of the ventilator.5. The system according to claim 4, wherein the at least one controlleris configured to determine, based on the LP signal, whether there issynchrony or asynchrony between respiratory phases of the ventilator andrespiratory phases of the patient, and to automatically adjust the levelof ventilatory assist and/or to signal that the level of ventilatoryassist should be adjusted only in case of synchrony between said phases.6. The system according to claim 2, wherein the at least one controlleris configured to determine an appropriate level of ventilatory assistbased on a LP signal response to at least one change in ventilatoryassist level.
 7. The system according to claim 1, wherein the controlleris configured to determine if the level of positive end-expiratorypressure (PEEP) currently applied to the patient should be adjusted,based on said at least one LP signal.
 8. The system according to claim7, wherein said at least one LP signal is an expiratory LP signalregistered during ventilator expiration, the at least one controller isconfigured to determine if the level of PEEP currently applied to thepatient should be adjusted based on the expiratory LP signal.
 9. Thesystem according to claim 8, wherein the at least one controller isconfigured to compare the expiratory LP signal with a threshold valueand, if the threshold value is exceeded, to automatically adjust thelevel of PEEP and/or to signal that the level of PEEP should be adjustedto an operator of the ventilator.
 10. The system according to claim 7,wherein the at least one controller is configured to determine whetherthere is synchrony or asynchrony between respiratory phases of theventilator and respiratory phases of the patient, and to automaticallyadjust the level of PEEP and/or to signal that the level of PEEP shouldbe adjusted only in case of synchrony between said phases.
 11. Thesystem according to claim 7, wherein the at least one controller isconfigured to determine an appropriate PEEP level based on a LP signalresponse to at least one change in PEEP level.
 12. The system accordingto claim 1, wherein the controller is configured to determine when toinitiate said inspiratory cycle-off by determining when said at leastone LP signal exceeds a certain threshold value serving as a triggerlevel for said inspiratory cycle-off.
 13. The system according to claim1, wherein the controller is configured to use said at least one LPsignal to detect the false-triggering of patient-triggered respirationphases and/or the reverse phase respiration.
 14. The system according toclaim 13, wherein said at least one LP signal is an inspiratory LPsignal registered during ventilator inspiration, and the at least onecontroller is configured to compare the inspiratory LP signal with athreshold value and, if said threshold value is exceeded, automaticallyadjust the operation of the ventilator to avoid or at least mitigate therisk of false-triggering and/or reverse phase respiration, and/or togenerate an alarm notifying the ventilator operator of the detectedfalse-triggering, and/or reverse phase respiration.
 15. The systemaccording to claim 13, wherein the at least one controller is configuredto use said at least one LP signal to detect false-triggering ofinspiration phases in a pneumatically controlled support mode or aneurally controlled mode.
 16. A system for use in connection withmechanical ventilation of a patient, provided by a ventilator, thesystem comprising: a bioelectric sensor arrangement configured toregister at least one bioelectric signal, hereinafter referred to as LPsignal, originating from and relating to muscular activity of at leastone muscle in the laryngopharyngeal region of said patient; and at leastone controller configured to control the operation of said ventilatorbased on said at least one LP signal, wherein the bioelectric sensorarrangement comprises: an oesophageal catheter having at least one LPelectrode configured to register said at least one LP signal in thelaryngopharyngeal region of the patient; and at least one diaphragmelectrode configured to register at least one other signal related tothe muscular activity of the patient's diaphragm, wherein theoesophageal catheter has a length along which the at least one LPelectrode and the at least one diaphragm electrode are positioned, theoesophageal catheter being configured such that said length and saidpositions cause said at least one LP electrode to be positioned in thelaryngopharyngeal region of the patient and the at least one diaphragmelectrode to be positioned in a diaphragmatic region of the patient,when the oesophageal catheter is inserted as intended into theoesophagus of the patient.
 17. The system according to claim 16, whereinsaid at least one controller is configured to use said at least one LPsignal together with the at least one other signal related to themuscular activity of the patient's diaphragm, in the control of theoperation of said ventilator.
 18. The system according to claim 17,wherein said at least one other signal related to the muscular activityof the patient's diaphragm is used as control signal to control theoperation of the ventilator, and the at least one controller isconfigured to use the at least one LP signal to validate the reliabilityof said at least one other signal.
 19. The system according to claim 17,further comprising: a signal processor configured to receive said atleast one LP signal and said at least one other signal, and to processsaid signals differently in order to derive, from the at least one LPsignal, a first processed signal indicative of the electrical activityof at least one muscle in the laryngopharyngeal region, and to derive,from the at least one other signal, a second processed signal indicativeof the electrical activity of the diaphragm.
 20. The system according toclaim 17, wherein said at least one controller is configured to use saidat least one LP signal to detect ventilator-patient asynchrony.
 21. Thesystem according to claim 1, wherein said at least one controller isconfigured to use said at least one LP signal to control the operationof said ventilator when operated in a support ventilation mode beingeither a pressure support mode, a volume support mode, or a NAVA mode.22. The system according to claim 1, wherein said at least onecontroller is configured to use said at least one LP signal to determinewhen to switch from one respiratory phase of the ventilator to another.23. The system according to claim 1, wherein the at least one registeredLP signal is related to muscular activity of the thyroarytenoid muscleand/or the cricothyroid muscle of the patient.
 24. The system accordingto claim 16, wherein said at least one controller is configured to usesaid at least one LP signal to control the operation of said ventilatorwhen operated in a support ventilation mode being either a pressuresupport mode, a volume support mode, or a NAVA mode.
 25. The systemaccording to claim 16, wherein said at least one controller isconfigured to use said at least one LP signal to determine when toswitch from one respiratory phase of the ventilator to another.
 26. Thesystem according to claim 16, wherein the at least one registered LPsignal is related to muscular activity of the thyroarytenoid muscleand/or the cricothyroid muscle of the patient.
 27. A method formechanically ventilating a patient with a ventilator, the methodcomprising: registering, by a bioelectric sensor arrangement, at leastone laryngopharyngeal (LP) signal originating from and relating tomuscular activity of at least one muscle in the laryngopharyngeal regionof said patient, and controlling, by at least one controller, theoperation of said ventilator based on said at least one LP signal,wherein the controlling comprises: determining if a level of ventilatoryassist currently provided to the patient should be adjusted, based onsaid at least one LP signal; or determining if a level of positiveend-expiratory pressure (PEEP) currently applied to the patient shouldbe adjusted, based on said at least one LP signal; or determining whento initiate an inspiratory cycle-off by determining when said at leastone LP signal exceeds a certain threshold value serving as a triggerlevel for said inspiratory cycle-off; or using said at least one LPsignal to detect false-triggering of patient-triggered respirationphases and/or reverse phase respiration.
 28. A non-transitorycomputer-readable data storage medium encoded with programminginstructions, said storage medium when loaded into a control computer ofa ventilator having a bioelectric sensor arrangement for registering atleast one laryngopharyngeal (LP) signal originating from and relating tomuscular activity of at least one muscle in the laryngopharyngeal regionof said patient, said programming instructions causing said controlcomputer to: receive, from said bioelectric sensor arrangement, said atleast one LP signal; and control operation of said ventilator based onsaid at least one LP signal, wherein the control comprises: determiningif a level of ventilatory assist currently provided to the patientshould be adjusted, based on said at least one LP signal; or determiningif a level of positive end-expiratory pressure (PEEP) currently appliedto the patient should be adjusted, based on said at least one LP signal;or determining when to initiate an inspiratory cycle-off by determiningwhen said at least one LP signal exceeds a certain threshold valueserving as a trigger level for said inspiratory cycle-off; or using saidat least one LP signal to detect false-triggering of patient-triggeredrespiration phases and/or reverse phase respiration.